glucose metabolism in pancrateic beta-cell via circadian clock genes DBP and E4BP4
| Project/Area Number |
26460489
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OHTA Yasuharu 山口大学, 医学部, 准教授(寄附講座等) (60448280)
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| Co-Investigator(Kenkyū-buntansha) |
田口 昭彦 山口大学, 医学(系)研究科(研究院), 助教 (20634744)
秋山 優 山口大学, 医学部附属病院, 助教 (90717547)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 体内時計 / 時計遺伝子 / インスリン分泌 / 2型糖尿病 / 小胞体ストレス / 膵β細胞 / 概日リズム / 生体リズム / DBPシグナル |
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| Outline of Final Research Achievements |
In Wfs1-/- Ay/a islets, Dbp expression decreased and E4bp4 expression increased, leading to reduced DBP transcriptional activity. Transgenic mice expressing E4BP4 under the control of the mouse insulin Ⅰ gene promoter (MIP), in which E4BP4 in β-cells is expected to compete with DBP for D-box, displayed remarkable glucose intolerance with severely impaired insulin secretion. Basal ATP/ADP ratios in MIP-E4BP4 islets were elevated without the circadian oscillations observed in wild-type islets. Neither elevation of the ATP/ADP ratio nor an intracellular Ca2+ response was observed after glucose stimulation. RNA expressions of genes involved in insulin secretion gradually increase in wild-type islets early in the feeding period. In MIP-E4BP4 islets, however, these increases were not observed. Molecular clock output DBP transcriptional activity, susceptible to ER stress, plays pivotal roles in β-cell priming for insulin release by regulating β-cell metabolism and gene expressions.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Clock Gene Dysregulation Induced by Chronic ER Stress Disrupts β-cell Function.2017
Author(s)
Ohta Y., Taguchi A., Matsumura T., Nakabayashi H., Akiyama M., Yamamoto K., Fujimoto R., Suetomi R., Yanai A., Shinoda K., Tanizawa Y.
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Journal Title
EBioMedicine
Volume: 18
Pages: 146-156
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features.2014
Author(s)
Matsunaga K, Tanabe K, Inoue H, Okuya S, Ohta Y, Akiyama M, Taguchi A, Kora Y, Okayama N, Yamada Y, Wada Y, Amemiya S, Sugihara S, Nakao Y, Oka Y, Tanizawa Y.
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Journal Title
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Clock gene dysregulation induced by chronic endoplasmic reticulum stress disrupts β-cell function2016
Author(s)
Yasuharu Ohta, Akihiko Taguchi, Takuro Matsumura, Hiroko Nakabayashi, Masaru Akiyama, Risa Suetomi, Akie Yanai, Koh Shinoda, Yukio Tanizawa
Organizer
11th IDF-WPR Congress & 8th AASD Scientific Meeting
Place of Presentation
Taipei International Convention Center, Taipei, Taiwan
Year and Date
2016-10-27
Related Report
Int'l Joint Research
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[Presentation] Clock gene dysreguration induced by chronic ER stress disrupts β-cell function2016
Author(s)
Yasuharu Ohta, Akihiko Taguchi, Takuro Matsumura, Hiroko Nakabayashi, Masaru Akiyama, Risa Suetomi, Akie Yanai, Koh Shinoda, Yukio Tanizawa
Organizer
The Islet Study Group meeting 2016
Place of Presentation
Riessersee Hotel Resort, Garmisch-Partenkirchen, Germany
Year and Date
2016-09-16
Related Report
Int'l Joint Research
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